The Rad17 homologue of Arabidopsis is involved in the regulation of DNA damage repair and homologous recombination

Abstract

SummaryRad17 is involved in DNA checkpoint control in yeast and human cells. A homologue of this gene as well as other genes of the pathway (the 9-1-1 complex) are present in Arabidopsis and share conserved sequence domains with their yeast and human counterparts. DNA-damaging agents induce AtRAD17 transcriptionally. AtRAD17 mutants show increased sensitivity to the DNA-damaging chemicals bleomycin and mitomycin C (MMC), which can be reversed by complementation, suggesting that the loss of function of Rad17 disturbs DNA repair in plant cells. Our results are further con®rmed by the phenotype of a mutant of the 9-1-1 complex (Rad9), which is also sensitive to the same chemicals. AtRAD9 and AtRAD17 seem to be epistatic as the double mutant is not more sensitive to the chemicals than the single mutants. The mutants show a delay in the general repair of double-strand breaks (DSBs). However, frequencies of intrachromosomal homologous recombination (HR) are enhanced. Nevertheless, the mutants are pro®cient for a further induction of HR by genotoxic stresses. Our results indicate that a mutant Rad17 pathway is associated with a general deregulation of DNA repair, which seems to be correlated with a de®ciency in non-homologous DSB repair.

SUPPRESSOR OF GAMMA RESPONSE1 Links DNA Damage Response to Organ Regeneration

“…Similarly, brca1 mutants show enhanced cell death to Mitomycin C, a DNA cross linker (Horvath et al, 2017). DNA damage-induced hypersensitivity was also observed for mutants in PARP1,2 (Song et al, 2015) and RAD17 (Heitzeberg et al, 2004) in response to bleomycin and Mitomycin C; these genes are also damage-induced by SOG1 (Culligan et al, 2006), with a function in an alternative, microhomology-mediated nonhomologous end-joining repair pathway, and in ssDNA-sensing for checkpoint control, respectively (Shrivastav et al, 2008;Hu et al, 2016).…”

Epigenetic Regulation, Somatic Homologous Recombination, and Abscisic Acid Signaling Are Influenced by DNA Polymerase ϵ Mutation inArabidopsis

“…defective in a calcium binding EF-hand protein) ; while mutation in BRU1 (a novel protein involved in DNA repair and replication) (Takeda et al, 2004), RAD50 (Gherbi et al, 2001), RAD17, or RAD9 (Heitzeberg et al, 2004) only slightly increases HR, whereas teb (a homolog of human DNA polymerase u) (Inagaki et al, 2006), rad51c, or rad51d (a bacterial RecA recombinase homolog) (Durrant et al, 2007), mim (hypersensitive to MMS, irradiation, and MMC, a structural maintenance of chromosome protein) (Mengiste et al, 1999;Hanin et al, 2000), and ino80 (an ortholog of the SWI/SNF ATPase family) mutations apparently decreased HR. We also observed that mutations in ROR1/RPA2A elevated the HR to a similar level as in abo4 mutants (see Supplemental Figure 2 online).…”

Ribonucleotide Reductase Regulation in Response to Genotoxic Stress in Arabidopsis

“…Our experiments were performed in various mutants that were already characterized: the atr-3 2/2 and atm-2 2/2 null mutants (Garcia et al, 2003;Culligan et al, 2004), the rad9-1 and rad17-1 mutants (Heitzeberg et al, 2004), as well as the tso2-1 2/2 and rnr2a-1 2/2 ethyl methanesulfonate mutants (Wang and Liu, 2006 …”

“…Other checkpoint proteins were also identified in Arabidopsis, such as AtRAD17 and AtRAD9 (Heitzeberg et al, 2004) that are epistasic in the DSB response. An ATM-dependent transcriptional regulation of AtRAD17 was also shown in response to g-irradiation (Culligan et al, 2006;Ricaud et al, 2007).…”